Stool screening for colorectal cancer: evolution from occult blood to molecular markers

Background: Colorectal cancer is the second leading cause of malignant death, and better preventive strategies are needed. Participation rates for colorectal cancer screening remain low due, in part, to perceived discomfort, potential harm, and high costs with available tools. Methods: Stool testing, unlike other conventional screening approaches, is noninvasive and requires no cathartic preparation. However, widely used fecal blood tests yield frequent false-negative and false-positive results that lower screening effectiveness and raise program costs. There is a compelling biological rationale to target DNA alterations exfoliated from neoplasms into stool, and multiple DNA markers would need to be assayed because of the genetic heterogeneity of colorectal neoplasia. Early clinical studies with this multi-target DNA-based stool assay approach suggest high sensitivity for both colorectal cancer and premalignant adenomatous polyps while maintaining high specificity. Conclusions: This apparently accurate and user-friendly new approach holds promise to improve the effectiveness, efficiency, and appeal of colorectal cancer screening. Large-scale clinical studies are clearly warranted to corroborate the early results.